Enhancing Respiratory Motor Function after Spinal Cord Injury

增强脊髓损伤后的呼吸运动功能

基本信息

  • 批准号:
    10323658
  • 负责人:
  • 金额:
    $ 57.82万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2019
  • 资助国家:
    美国
  • 起止时间:
    2019-01-01 至 2023-03-31
  • 项目状态:
    已结题

项目摘要

ABSTRACT The proposed studies exploit exciting new developments in neuroplasticity to enhance recovery of ventilatory- related diaphragm muscle (DIAm) activity following cervical spinal cord injury. There are nearly 17,000 new cases of spinal cord injury in the United States each year, with around 282,000 people affected. The majority of these injuries involve the cervical spinal cord and result in significant impairment of ventilatory-related DIAm activity and an inability to maintain adequate ventilation. Long-term dependence on mechanical ventilation is associated with significant morbidity and mortality. Thus, enhancing recovery of ventilatory-related DIAm activity following cervical spinal cord injury is highly significant. Upper-cervical (C1-C3) spinal cord injury disrupts direct excitatory descending bulbospinal glutamatergic (Glu) input to phrenic motor neurons (PhMNs). Importantly, most spinal cord injuries are incomplete, thus spared descending pathways to PhMNs are an extant substrate for neuroplasticity to restore DIAm activity, either by increasing excitatory (Glu) nerve terminal density and/or by altering postsynaptic Glu receptor (NMDA NR1) expression. In the proposed studies, we will employ a well-established C2 spinal hemisection (C2SH) model of incomplete spinal cord injury in rats, in which spontaneous recovery of ventilatory-related DIAm activity occurs in a BDNF/TrkB signaling-dependent fashion. Previously, we found that C2SH impairs ventilatory-related DIAm behaviors, which require recruitment of smaller (more excitable) PhMNs comprising fatigue resistant motor units. These ventilatory-related behaviors only partially recover over time, whereas, surprisingly, there is near full recovery of higher force airway clearance behaviors, which require recruitment of larger (less excitable) PhMNs comprising more fatigable motor units. The overall hypothesis of the proposed research is that the mechanisms underlying neuroplasticity and recovery of ventilatory-related DIAm activity after C2SH depend on PhMN size (more pronounced in smaller PhMNs), are mediated by NMDA Glu neurotransmission, and are promoted by BDNF/TrkB signaling. Three specific aims are proposed: 1) To determine the effect of BDNF/TrkB signaling on Glu presynaptic terminal density at PhMNs of differing size after C2SH; 2) To determine the effect of BDNF/TrkB signaling on NMDAR expression at PhMNs of differing size after C2SH; and 3) To determine whether NMDARs underlie the effects of BDNF/TrkB signaling on recovery of ventilatory-related DIAm activity after C2SH. The results of the proposed studies will guide development of effective therapeutic approaches to enhance recovery of respiratory function in patients with incomplete spinal cord injury.
摘要

项目成果

期刊论文数量(0)
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Carlos B Mantilla其他文献

Carlos B Mantilla的其他文献

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{{ truncateString('Carlos B Mantilla', 18)}}的其他基金

Prediction and early recognition of opioid-induced respiratory depression
阿片类药物引起的呼吸抑制的预测和早期识别
  • 批准号:
    10426828
  • 财政年份:
    2022
  • 资助金额:
    $ 57.82万
  • 项目类别:
Prediction and early recognition of opioid-induced respiratory depression
阿片类药物引起的呼吸抑制的预测和早期识别
  • 批准号:
    10593973
  • 财政年份:
    2022
  • 资助金额:
    $ 57.82万
  • 项目类别:
Enhancing Respiratory Motor Function after Spinal Cord Injury
增强脊髓损伤后的呼吸运动功能
  • 批准号:
    10675888
  • 财政年份:
    2019
  • 资助金额:
    $ 57.82万
  • 项目类别:
Enhancing Respiratory Motor Function after Spinal Cord Injury
增强脊髓损伤后的呼吸运动功能
  • 批准号:
    10083760
  • 财政年份:
    2019
  • 资助金额:
    $ 57.82万
  • 项目类别:
Mechanisms of age-related susceptibility of NMJ function
NMJ 功能与年龄相关的易感性机制
  • 批准号:
    10161705
  • 财政年份:
    2017
  • 资助金额:
    $ 57.82万
  • 项目类别:
Mechanisms of age-related susceptibility of NMJ function
NMJ 功能与年龄相关的易感性机制
  • 批准号:
    9921270
  • 财政年份:
    2017
  • 资助金额:
    $ 57.82万
  • 项目类别:
Respiratory Control in Old Age
老年呼吸控制
  • 批准号:
    8871511
  • 财政年份:
    2013
  • 资助金额:
    $ 57.82万
  • 项目类别:
Respiratory Control in Old Age
老年呼吸控制
  • 批准号:
    10740986
  • 财政年份:
    2013
  • 资助金额:
    $ 57.82万
  • 项目类别:
Respiratory Control in Old Age
老年呼吸控制
  • 批准号:
    8665855
  • 财政年份:
    2013
  • 资助金额:
    $ 57.82万
  • 项目类别:
Respiratory Control in Old Age
老年呼吸控制
  • 批准号:
    9895586
  • 财政年份:
    2013
  • 资助金额:
    $ 57.82万
  • 项目类别:

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